Microfocused Nanoparticulate ions to enable intracellular molecular imaging.

微聚焦纳米颗粒离子可实现细胞内分子成像。

• 批准号: 8059377
• 负责人: John Albert Schultz
• 金额: $ 79.99万
• 依托单位: IONWERKS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059377
• 关键词: Ablation; Alloys; Caliber; Cations; Cell Line; Cell Volumes; Cell surface; Cells; Characteristics; Chemicals; Deposition; Development; Family; Gases; Glycolipids; Glycopeptides; Goals; Gold; Height; Helium; Image; Imaging Techniques; Implant; Ions; Lasers; Legal patent; Mass Spectrum Analysis; Measures; Metals; Methodology; Methods; Molecular; Molecular Profiling; Outcome; Particle Size; Particulate; Phase; Preparation; Research; Resolution; Risk; Sales; Signal Transduction; Solid; Spectrometry, Mass, Secondary Ion; Structure of molecular layer of cerebellar cortex; Surface; System; Techniques; Time; Tissues; Width; design; detector; implantation; innovation; instrument; instrumentation; ion mobility; ionization; mass spectrometer; molecular imaging; monolayer; nanometer; nanoparticulate; novel; organic acid; particle; submicron; tissue preparation; two-dimensional

DESCRIPTION (provided by applicant): Within the volume of a single cell, lines an extensive amount of information. The current scope of molecular imaging using mass spectrometry typically swamps the cell volume with organic acid matrix just to get observable signals. Herein lies the problem. Putting more matrix that there is analyte (i.e. cellular volume) inherently makes intracellular imaging via organic acids improbable. Therefore, Ionwerks has developed a comprehensive set of instrumentation, and nanoparticulate preparation techniques which combine two dimensional ion-mobility mass spectrometry and nanoparticulate tissue preparation which provide a means to analysis of tissues while preserving their histological attributes. Our research has demonstrated that sub-monolayers of nanoparticulates implanted into various depths within a tissue, provide agreeable signal levels. This means, the particulate to analyte ratio is much less that typical preparations: the chemical information is preserved and observable. The nanoparticulates will also be microfocused to allow for unique molecular secondary ion mass spectrometry (SIMS). Furthermore, we are developing small format oTOF MS detectors which can be combined with leading edge surface imaging techniques to create a one of a kind imaging platform from which surfaces / tissues can be morphologically imaged, and mass spectra of ejected ions can be recorded. PUBLIC HEALTH RELEVANCE: The goal of this project is implant histological prepared tissues with gold nanoparticulates, then to measure the ejected ions using a low profile oTOF-MS system from a microfocused nanoparticulate beam. This project will lay the groundwork for utilizing the helium ion-beam microprobe systems as a combined topographical imaging system, as well as molecular imaging systems.

描述（由申请人提供）：在单个细胞的体积内，排列着大量的信息。当前使用质谱的分子成像范围通常会用有机酸基质淹没细胞体积，只是为了获得可观察的信号。问题就在这里。放置比分析物（即细胞体积）更多的基质本身就不可能通过有机酸进行细胞内成像。因此，Ionwerks 开发了一套全面的仪器和纳米颗粒制备技术，将二维离子淌度质谱和纳米颗粒组织制备相结合，提供了一种分析组织的方法，同时保留其组织学属性。我们的研究表明，植入组织内不同深度的纳米颗粒亚单层可提供令人满意的信号水平。这意味着，颗粒与分析物的比率远低于典型制剂：化学信息得以保存并可观察。纳米颗粒也将被微聚焦，以实现独特的分子二次离子质谱（SIMS）。此外，我们正在开发小型 oTOF MS 探测器，它可以与领先的表面成像技术相结合，创建一种独一无二的成像平台，可以对表面/组织进行形态成像，并可以记录喷射离子的质谱。 公共健康相关性：该项目的目标是用金纳米颗粒植入组织学准备的组织，然后使用低剖面 oTOF-MS 系统从微聚焦纳米颗粒束中测量喷射的离子。该项目将为利用氦离子束微探针系统作为组合地形成像系统以及分子成像系统奠定基础。